FDA Accepts Investigational New Drug Application for ARI-3037MO; First in Man Clinical Trial to Begin During First Quarter of 2011

- ARI-3037MO is a once-daily, niacin analog being developed for treatment of dyslipidemia

- ARI-3037MO produced compelling changes in lipids (e.g., greater than 70% reduction in triglycerides and LDL-cholesterol) in preclinical studies

- ARI-3037MO did not induce flushing in nonclinical pharmacology/toxicology experiments

- Nonclinical drug safety studies demonstrate ARI-3037MO has high therapeutic index

- First-in-man clinical trial is expected to begin by the end of the first quarter of 2011

Mar 21, 2011, 21:00 ET from Arisaph Pharmaceuticals, Inc.

BOSTON, March 21, 2011 /PRNewswire/ -- Arisaph Pharmaceuticals, Inc., a privately held drug discovery biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Company's recently submitted Investigational New Drug (IND) application to evaluate ARI-3037MO in a phase I human clinical trial in healthy volunteers.  ARI-3037MO, a proprietary new chemical entity, is a once-daily, niacin analog being developed for the treatment of dyslipidemia. In preclinical pharmacology studies, the compound produced greater lipid responses than niacin in a relevant animal model of hyperlipidemia.  Additionally, ARI-3037MO showed an extremely favorable safety profile, including the absence of flushing, in non-clinical drug safety studies. The Company believes that an efficacious and well tolerated niacin analog will be more widely utilized than existing forms of niacin in treating hypercholesterolemia, a disorder that afflicts as many as 93 million Americans according to data published by the American Heart Association.(1)

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"The FDA's acceptance of our IND is a major milestone for Arisaph, particularly considering that we developed the compound from lead selection to IND filing in about 9 months," said Christopher P. Kiritsy, President and Chief Executive Officer of Arisaph Pharmaceuticals.  "With ARI-3037MO, we have designed a once a day, structural analog of niacin that retains niacin's beneficial biological effects on lipids without producing the irritating side effect of flushing."    

As part of the IND submission, Arisaph completed comprehensive nonclinical drug safety studies, including 28-day toxicology studies in rats and dogs.  The results show that ARI-3037MO has a favorable safety pharmacology profile and a wide therapeutic index.  One of the major challenges with current forms of niacin is that they are dose limited because of adverse side effects, such as gastrointestinal intolerance, liver enzyme elevations and flushing. The Company believes that ARI-3037MO can produce greater therapeutic benefits than existing forms of niacin as a result of mitigating such adverse side effects.  

In preclinical studies involving hamsters fed a high-fat diet, ARI-3037MO showed robust changes in lipids, including LDL and HDL cholesterols and triglycerides (TGs).  Specifically, once-daily treatments of ARI-3037MO lowered both LDL cholesterol and TGs greater than 70% from placebo.  In comparison, higher doses of niacin reduced LDL cholesterol and TGs approximately 50% from placebo.  Additionally, ARI-3037MO increased the proportion of HDL cholesterol to a greater extent than niacin.  ARI-3037MO treated hamsters showed a significant increase in ATP-binding cassette transporter A1 (ABCA1), apolipoprotein A-1 (ApoA1), and adiponectin compared to the vehicle control animals.  The ABCA1 and ApoAI increases are noteworthy, as the proteins that result from these transcripts are involved in the synthesis and maturation of HDL.  

"Significant lipid changes coupled with the increased mRNA levels for certain regulatory proteins involved in HDL synthesis and reverse cholesterol transport offers compelling evidence to support the mechanism based efficacy of this niacin analog," commented, Dr. Ernst Schaefer, Professor of Medicine, Tufts University School of Medicine. "The availability of an effective and tolerable niacin replacement would be a major advancement for the treatment of mixed lipid disorders."

In addition to the compelling preclinical efficacy, ARI-3037MO did not induce "flushing" as measured by changes in capillary blood flow via the ear in mice. Such capillary blood flow measurements have translated well in evaluating the effects of niacin on flushing in human clinical trials. Additionally, flushing was not observed during clinical observations in 28-day rat and dog toxicological studies or in several other nonclinical studies, in which ARI-3037MO was administered in various doses to multiple species.  Flushing, representative of tingling and/or redness of the skin, is the principal side effect of niacin and in some patients can be extremely uncomfortable.  Consequently, many patients fail to achieve efficacious dosing or discontinue niacin therapy altogether, resulting in poor patient compliance and adherence.(2,3)  Based on preclinical results, the Company believes that ARI-3037MO represents an advancement in treating mixed lipid disorders in patients with coronary heart disease.

About Arisaph

Arisaph Pharmaceuticals Inc, an emerging biopharmaceutical company located in Boston, Massachusetts, was founded by Dr. William Bachovchin (Professor of Biochemistry, Tufts University School of Medicine), Christopher Kiritsy (Former EVP Corporate Development and CFO Kos Pharmaceuticals, Inc.) and Michael Jaharis (Founder, Chairman Emeritus, Kos Pharmaceuticals, Inc.) to develop differentiated therapies for cardiometabolic diseases and cancer.  Arisaph employs rational drug design approaches to develop differentiated new chemical entities (NCEs) that are highly potent and act on select, validated targets. By focusing its drug development activities on validated targets, the Company believes that the risks associated with new chemical entity development can be mitigated compared with developing first-in-class compounds for nonvalidated targets.  Arisaph has developed a rich pipeline of products at various stages of preclinical development, including a tumor activated prodrug platform being developed for both liquid and solid tumors.  The Company's vision is to create a fully integrated pharmaceutical company leveraging its drug discovery expertise to develop transformational, patent protected, medicines that offer distinct safety, efficacy and/or tolerability benefits compared with existing therapies for large markets, whose needs are not being fully met by current therapeutics.  

About Niacin Analog Program

The natural B vitamin niacin is a well known lipid lowering agent and has been used to treat mixed lipid disorders for over 50 years.  Niacin is recommended as a first-line drug for the treatment of hyperlipidemia and it is used in combination with statins to further reduce LDL cholesterol or to increase HDL cholesterol in patients with depressed HDL cholesterol levels.  Niacin can produce changes in HDL cholesterol up to 35%, lower LDL cholesterol up to 25% and lower triglycerides up to 50%.  Despite niacin's broad lipid altering profile, the use of niacin based therapies is diminished because of unpleasant side effects, particularly flushing.  Flushing, representative of tingling and/or redness of the skin, is the principal side effect of niacin and in some patients can be extremely uncomfortable.  Arisaph has developed a novel and proprietary class of structural analogs of niacin that produce compelling changes in lipids without provoking flushing as shown in preclinical pharmacology studies.

Certain statements in this press release, including statements regarding the Company's research and development effort, the Company's expectation to initiate human clinical studies, the Company's ability to finance its development programs into human clinical testing, and the Company's ability to successfully capitalize on the early stage research are subject to risks and uncertainties, which could cause the Company's actual results and the timing of certain events to differ materially from the Company's expectations. These risks and uncertainties include risks and uncertainties related to:  our ability to discover and develop new compounds and products using a novel approach to drug discovery; the early stage of all of our discovery and development efforts; our ability to complete preclinical and clinical development of our products; our ability to obtain and maintain regulatory approvals for our products; competition from other technologies and technologies similar to ours; obtaining, maintaining and protecting intellectual property utilized by our products; changes in legislation and regulations affecting our products and potential product candidates; our need to obtain additional funding to support our business activities; our dependence on collaborators and other third parties for development, manufacture, marketing, sales and distribution of products; the ability of our licensees to achieve developmental, regulatory and other milestones and to commercialize their products; the effect of conditions in the pharmaceutical industry and the economy in general, as well as certain other risks and uncertainties.

1. NHANES IV Data, American Heart Association, Heart Disease and Stroke Statistics – 2005
2. Kamal Bahl et al., American Journal of Cardiology, 2007; vol. 99, pages 530-534.
3. Davidson, M.H., American Journal of Cardiology, 2008; vol. 101[suppl], pages 14B–19B

SOURCE Arisaph Pharmaceuticals, Inc.